ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.826T>C (p.Cys276Arg) (rs879254692)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000238233 SCV000295001 likely pathogenic Familial hypercholesterolemia 1 2016-03-25 criteria provided, single submitter literature only
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix RCV000238233 SCV000503241 likely pathogenic Familial hypercholesterolemia 1 2016-12-16 criteria provided, single submitter clinical testing subjects mutated among 2600 FH index cases screened = 2 / FH-Ceva / Software predictions: Damaging
Integrated Genetics/Laboratory Corporation of America RCV000781499 SCV000919579 uncertain significance not specified 2017-11-10 criteria provided, single submitter clinical testing Variant summary: The LDLR c.826T>C (p.Cys276Arg) variant involves the alteration of a conserved nucleotide that results in the alteration of a cysteine residue at the protein level that is highly conserved across species (Bertolini 2013). The variant is located in the ligand-binding domain of the LDL receptor (InterPro). 4/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index), however these predictions have not been evaluated for functional impact by in vivo/vitro studies. This variant is absent in 246246 control chromosomes (gnomAD). The variant has been reported in individuals presented with hypercholesterolemia in heterozygous form (Bertolini 2003), however without providing clear evidence for causality. One clinical diagnostic laboratoy and a databases classified this variant as likely pathogenic, without evidence for independent evaluation. Variants involving the same codon such as C276G, C276F, C276W, and C276Y have been reported in affected individuals suggesting the functional importance of this codon. Taken together, this variant is classified as VUS-possibly pathogenic, until additional evidence becomes available.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.